title: Carcinoembryonic antigen-related cell adhesion molecule 16 interacts with alpha-tectorin and is mutated in autosomal dominant hearing loss (DFNA4).
abstract: We report on a secreted protein found in mammalian cochlear outer hair cells (OHC) that is a member of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family of adhesion proteins. Ceacam16 mRNA is expressed in OHC, and its protein product localizes to the tips of the tallest stereocilia and the tectorial membrane (TM). This specific localization suggests a role in maintaining the integrity of the TM as well as in the connection between the OHC stereocilia and TM, a linkage essential for mechanical amplification. In agreement with this role, CEACAM16 colocalizes and coimmunoprecipitates with the TM protein α-tectorin. In addition, we show that mutation of CEACAM16 leads to autosomal dominant nonsyndromic deafness (ADNSHL) at the autosomal dominant hearing loss (DFNA4) locus. In aggregate, these data identify CEACAM16 as an α-tectorin-interacting protein that concentrates at the point of attachment of the TM to the stereocilia and, when mutated, results in ADNSHL at the DFNA4 locus.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.forename: Katharine K
authors.initials: KK
authors.lastname: Miller
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hildebrand
authors.forename: A Eliot
authors.initials: AE
authors.lastname: Shearer
authors.forename: Adam P
authors.initials: AP
authors.lastname: DeLuca
authors.forename: Todd E
authors.initials: TE
authors.lastname: Scheetz
authors.forename: Jennifer
authors.initials: J
authors.lastname: Drummond
authors.forename: Steve E
authors.initials: SE
authors.lastname: Scherer
authors.forename: P Kevin
authors.initials: PK
authors.lastname: Legan
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Goodyear
authors.forename: Guy P
authors.initials: GP
authors.lastname: Richardson
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Cheatham
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Smith
authors.forename: Peter
authors.initials: P
authors.lastname: Dallos
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000378:metabolism; D005799:Genes, Dominant; D034381:Hearing Loss / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D024462:Myosin Type II / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D058851:GPI-Linked Proteins; D018995:Myosin Heavy Chains; D024462:Myosin Type II; D012333:RNA, Messenger; C575021:CEACAM16 protein, mouse; C477830:MYH7b protein, human; C491350:TECTA protein, human; C558358:CEACAM16 protein, human